Disorders of the Central Nervous System (CNS) can be medically treated in various ways. Of increasing importance in this regard are psychotropic drugs. But while such drugs have therapeutic effect, they also may cause unwanted and serious side effects. For example, schizophrenia can be treated with so-called typical drugs, which have been theorized to block certain dopamine (D2) receptors in the brain thought responsible for the positive symptoms of delusions, disordered thinking and the like. However, while these drugs can ameliorate some of the positive symptoms, they can also adversely affect the motor system, causing muscle problems such as spasms, cramps, tremors and Parkinsonism. Inasmuch as these types of side effects—generally characterized as Extrapyramidal Symptoms (EPS)—can be severe enough to disrupt daily activities, resort has been made to so-called atypical drugs.
Atypical antipsychotics have reduced incidents of EPS and can alleviate not only some of the positive symptoms of schizophrenia, but some of the negative symptoms as well, such as emotional unresponsiveness, social withdrawal and the like. Although antipsychotic drugs are believed to be more selective in their chemical effect on the brain, thereby reducing EPS, they too may have side effects. While these are not often as disruptive as those presented by typical drug therapy, they may nonetheless be of consequence to the patient. For example, atypical drugs can be sedating and can cause weight gain.
The situation is further complicated when several CNS disorders are present in a patient. For example, psychosis, such as schizophrenia, can often co-exist with depression, anxiety, obsessive-compulsive disorder (OCD) and other such illnesses. In such cases, treatment often entails the administration of a combination of drugs, e.g., one to treat schizophrenia and one to treat depression or other co-morbid CNS ailment. Because each such drug has its own side effects, the combined administration can lead to a multiplication or enhancement of same, all to the detriment of the patient. Moreover, it is theorized that a different brain receptor, or combination or permutation of receptors, are somehow implicated in each of the various CNS disorders; for example, schizophrenia has been thought to involve D2 and 5HT-2A receptors whereas depression has been associated with 5HT-1B receptors. A class of aminomethylphenoxymethyl/benzisoxazole substituted azabicyclic compounds, useful as selective agonists and antagonists of serotonin 1 (5-HT1) receptors, is described in WO 99/52907 to Bright.
It has hitherto proven difficult to find a single drug that can treat a patient suffering from diverse CNS disorders where a plurality of different receptors are in play. Accordingly, there is an on-going need for a psychotropic drug that has a pronounced reduction in side effects, and that can efficaciously and by itself treat multiple CNS disorders in which an antagonist or agonist to different receptors is indicated. Specifically, it would be desirable to find a drug that can concurrently treat schizophrenia and depression in which D2, 5HT-2A and 5HT-1B receptors are involved.